A Study of ABI-2280 Vaginal Tablet in Participants With Cervical Intraepithelial Neoplasia

Cervical Intraepithelial Neoplasia Clinical Trial

Official title:

An Open-Label Single and Multiple-dose, Study to Evaluate Safety, Tolerability and Efficacy of ABI-2280 Vaginal Tablet in Participants With Cervical Squamous Intraepithelial Lesions

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05502367
• Other study ID #: ABI-2280-303
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 10, 2022
• Est. completion date: May 31, 2024

Study information

• Verified date: July 2023
• Source: Antiva Biosciences
• Contact: Oranee Daniels, MD
• Phone: 650-822-1400
• Email: odaniels[@]antivabio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label study to evaluate the safety, tolerability, and efficacy of ABI-2280 in participants with cervical squamous intraepithelial lesions. This study is divided into 2 parts - Part A and Part B.

Part A consists of 3 dose escalating cohorts. Part B is a dose expansion cohort.

Participants will self-administer ABI-2280.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 29
• Est. completion date: May 31, 2024
• Est. primary completion date: April 1, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 25 Years to 55 Years

Eligibility

Inclusion Criteria:

• Women, 25 to 55 years old.

• For Part A, participants with biopsy-confirmed CIN (with visible lesions) regardless of p16 positivity may be enrolled upon consultation with PI and medical Monitor. These participants will not be required to get large loop excision of the transformation zone (LLETZ) if not medically necessary, as determined by the PI in consultation with the Medical Monitor.

• For Part B, biopsy-confirmed cervical HSIL that is p16+ (p16INK4a expressed) within 60 days of enrollment (dosing) with no evidence of invasive cancer in any specimen. If biopsy was performed more than 60 days before planned enrollment, participants must agree to have another biopsy performed at the Screening visit, unless approved by the Medical Monitor.

• No prior treatment for Cervical intraepithelial neoplasia (CIN).

• Generally, in good health with no clinically significant pulmonary, cardiac, gastro-enterologic, neurologic, renal, musculoskeletal, rheumatologic, metabolic, neoplastic, or endocrine disease.

Exclusion Criteria:

• Women who are pregnant, plan to become pregnant in the next 4 months, or lactating females.

• Unwilling to use stringent methods of contraception (including barrier method, as well as another acceptable method) throughout the course of the study.

• History of cancer, except basal cell or squamous cell carcinoma of the skin.

• History of genital herpes with outbreak within prior 12 months.

• Have an active pelvic or non-HPV (Human papillomavirus) vaginal infection (e.g., that was detected by a positive urine screen for gonorrhea or chlamydial infection, bimanual exam consistent with pelvic inflammatory disease, positive bedside testing criteria for bacterial vaginosis, candida vaginitis or trichomonal vaginitis, etc).

• Current or recent abnormal vaginal discharge and /or abnormal vaginal bleeding.

• Had a therapeutic abortion or miscarriage less than 3 months prior.

• Any clinically significant immune suppressing condition.

• Participants with a significant acute condition or any other condition that in the opinion of the Investigator might interfere with the evaluation of the study objectives.

• Women who, in the PI's judgment, would be harmed by the delay in undergoing definitive treatment as a result of study participation and the ABI-2280 Vaginal Tablet dosing schedule.

Related Conditions & MeSH terms

• Carcinoma in Situ
• Cervical Intraepithelial Neoplasia
• Neoplasms
• Uterine Cervical Dysplasia

Intervention

Drug:
• ABI-2280
Vaginal Tablet

Locations

Country	Name	City	State
Australia	East Sydney Doctors	Darlinghurst	New South Wales
Australia	Gold Coast University Hospital	Southport	Queensland
South Africa	Farmvos	Bloemfontein	Free State

Sponsors (1)

Lead Sponsor	Collaborator
Antiva Biosciences

Countries where clinical trial is conducted

Australia,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events (Safety and Tolerability)	For Parts A and B, to assess the safety and tolerability of ABI-2280 Vaginal Tablet by the incidence and severity of Adverse events (AEs).	From Baseline to Day 42 post dose administration
Secondary	Pharmacokinetics of ABI-2280 after single and multiple doses	Time to maximum observed drug concentration (tmax)	60 minutes prior to dosing on Day 1, and 1 hour (± 5 mins) and 6 hours (± 1 hour) post-dose on Day 1. For Part A, additional samples will be taken at 2 hours (± 5 mins) and 24 hours (± 2 hours) post dose on Day 1.
Secondary	Pharmacokinetics of ABI-2280 after single and multiple doses	Maximum observed drug concentration (Cmax)	60 minutes prior to dosing on Day 1, and 1 hour (± 5 mins) and 6 hours (± 1 hour) post-dose on Day 1. For Part A, additional samples will be taken at 2 hours (± 5 mins) and 24 hours (± 2 hours) post dose on Day 1.
Secondary	Pharmacokinetics of ABI-2280 after single and multiple doses	Area under the curve (AUC) from time zero to last measurable concentration (AUC0-last)	60 minutes prior to dosing on Day 1, and 1 hour (± 5 mins) and 6 hours (± 1 hour) post-dose on Day 1. For Part A, additional samples will be taken at 2 hours (± 5 mins) and 24 hours (± 2 hours) post dose on Day 1.
Secondary	Pharmacokinetics of ABI-2280 after single and multiple doses	AUC from time zero to infinity (AUC8)	60 minutes prior to dosing on Day 1, and 1 hour (± 5 mins) and 6 hours (± 1 hour) post-dose on Day 1. For Part A, additional samples will be taken at 2 hours (± 5 mins) and 24 hours (± 2 hours) post dose on Day 1.
Secondary	Pharmacokinetics of ABI-2280 after single and multiple doses	Apparent elimination half-life (t½)	60 minutes prior to dosing on Day 1, and 1 hour (± 5 mins) and 6 hours (± 1 hour) post-dose on Day 1. For Part A, additional samples will be taken at 2 hours (± 5 mins) and 24 hours (± 2 hours) post dose on Day 1.
Secondary	Pharmacokinetics of ABI-2280 after single and multiple doses	Apparent terminal elimination rate constant (Kel)	60 minutes prior to dosing on Day 1, and 1 hour (± 5 mins) and 6 hours (± 1 hour) post-dose on Day 1. For Part A, additional samples will be taken at 2 hours (± 5 mins) and 24 hours (± 2 hours) post dose on Day 1.
Secondary	Pharmacokinetics of ABI-2280 after single and multiple doses	Apparent clearance (CL/F)	60 minutes prior to dosing on Day 1, and 1 hour (± 5 mins) and 6 hours (± 1 hour) post-dose on Day 1. For Part A, additional samples will be taken at 2 hours (± 5 mins) and 24 hours (± 2 hours) post dose on Day 1.
Secondary	Pharmacokinetics of ABI-2280 after single and multiple doses	Apparent volume of distribution at the terminal phase (Vz/F)	60 minutes prior to dosing on Day 1, and 1 hour (± 5 mins) and 6 hours (± 1 hour) post-dose on Day 1. For Part A, additional samples will be taken at 2 hours (± 5 mins) and 24 hours (± 2 hours) post dose on Day 1.
Secondary	Histopathologic changes in cHSIL by large loop excision of the transformation zone (LLETZ) specimen	To assess histopathologic changes in cHSIL by LLETZ	12 weeks after the first dose of ABI-2280 Vaginal Tablet